Ultrasound- and NIR-Responsive Polydextran/Black TiO(2) Nanocomposite Hydrogels for Triple-Modal Antibacterial Therapy.

Titanium dioxide (TiO(2))-containing nanocomposite hydrogels have shown great promise in biomedical applications, where TiO(2) nanoparticles serve as sensitizers to generate reactive oxygen species (ROS) in sonodynamic therapy (SDT) and photodynamic therapy (PDT). Nevertheless, the limited bandgap of TiO(2) nanoparticles restricts activation to ultraviolet light, and the recombination of electron-hole pairs diminishes ROS production efficiency. Here, an innovative TiO(2)-containing nanocomposite hydrogel is developed by incorporating black TiO(2) (bTiO(2)) nanoparticles into a hydrazone-cross-linked polymeric network of polydextran aldehyde (PDA) and polydextran hydrazide (PDH). Particularly, bTiO(2) nanoparticles are further functionalized with amino groups to form imine cross-links at the particle-polymer interface, enhancing their dispersion and also improving the mechanical properties of the network. The structures and properties of the bTiO(2)-containing PDA/PDH nanocomposite hydrogels are systematically investigated compared to the hydrogels featuring only a polymeric network and those based on white TiO(2) nanoparticles. The bTiO(2)-containing PDA/PDH nanocomposite hydrogels exhibit increased ROS generation and exceptional photothermal properties when exposed to ultrasound and near-infrared light, significantly boosting their antibacterial efficacy through a combination of SDT, PDT, and photothermal therapy (PTT). Taken together, bTiO(2)-containing PDA/PDH nanocomposite hydrogel is a versatile therapeutic platform that offers dual external stimuli-responsiveness and dynamic features for triple-modal antibacterial applications.